Taltz® ▼ (ixekizumab)

This information is intended for UK registered healthcare professionals only as a scientific exchange in response to your search for information. Please refer to the link for full prescribing information: Taltz Summary of Product Characteristics (SmPC)

Taltz® ▼ (ixekizumab): Long-Term Safety in Psoriatic Arthritis

Exposure-adjusted IR for TEAEs and SAEs remained stable or decreased over time in ixekizumab clinical trials.

General Information

  • The long-term safety of ixekizumab has been evaluated in 1401 patients with PsA who received ixekizumab up to 3 years (2228.6 PYs). The safety profile is consistent with previous reports in patients who received ixekizumab for the treatment of PsO or PsA and the rates of reported AEs remained stable or decreased over time with continued ixekizumab exposure.1

  • Note that data from multiple, different dosing regimens, including unapproved doses, are included in this response.

  • Please find the approved dosing information and the full list of adverse drug reactions of ixekizumab in the Taltz summary of product characteristics.2

Phase 3 Clinical Trials

Incidence rates of TEAEs and SAEs from 3 phase 3 clinical trials with data through 96 weeks are illustrated in Figure 1. Among all ixekizumab exposures in PsA (data from SPIRIT-P1, -P2, and -P3; N=1118; PY=1373.4), the IR of overall TEAEs decreased with longer ixekizumab exposure. Some variation in SAE IRs were noted, but authors concluded that there was no clinically meaningful increase in the exposure-adjusted IR with longer ixekizumab exposures.3

As presented in Table 1, most TEAEs were mild-to-moderate in severity and few led to discontinuation. The most common TEAEs were ISR, upper respiratory tract infections, and nasopharyngitis.3

There was no increase in IRs of AESIs analyzed over 12-week intervals through 96 weeks, including 

  • infection-related TEAEs

  • ISR

  • MACE

  • hypersensitivity reactions

  • malignancy, and

  • depression-related events.3

One case each of UC and CD were reported. These were SAEs but did not lead to discontinuation of ixekizumab treatment. The CD event was reported as a new case, though the patient did have a history of irritable bowel syndrome. Of the 12 patients with preexisting conditions or a history of illness suggestive of IBD, none experienced disease exacerbation during ixekizumab treatment.3

Four deaths were reported. Causes of death were due to pneumonia, cerebrovascular accident, cardiorespiratory arrest, and drowning.3

Note: Cases of new or exacerbations of inflammatory bowel disease have been reported with ixekizumab. Ixekizumab is not recommended in patients with inflammatory bowel disease. If a patient develops signs and symptoms of inflammatory bowel disease or experiences an exacerbation of pre-existing inflammatory bowel disease, ixekizumab should be discontinued and appropriate medical management should be initiated.2

Figure 1. Incidence Rates of TEAEs and SAEs in the Double-blind Treatment Period and Integrated PsA Dataset4

Abbreviations: IR = incidence rate; IXE = ixekizumab; PBO = placebo; PsA = psoriatic arthritis; PY = patient-years; SAE = serious adverse event; TEAE = treatment-emergent adverse event.

aData are IR for 0-24 Weeks for the Double-blind Treatment Period (dotted line) for SPIRIT-P1 and -P2 only (inadequate responders excluded from week 16).

bData are mean IR by 12-week intervals to Week 96 for the Integrated PsA dataset (SPIRIT-P1, -P2, and -P3).

Table 1. Overview of Adverse Events, Integrated PsA Safety Dataset4

n (IR) [95% CI]

All PsA IXE
N=1118
PY=1373.4

1 TEAE

868 (63.2) [59.1, 67.5]

  • Mild

392 (28.5) [25.9, 31.5]

  • Moderate

396 (28.8) [26.1, 31.8]

  • Severe

80 (5.8) [4.7, 7.3]

1 SAE

91 (6.6) [5.4, 8.1]

Deaths

4 (0.3) [0.1, 0.8]

Discontinuations due to adverse event

80 (5.8) [4.7, 7.3]

Abbreviations: IR = incidence rate; IXE = ixekizumab; PsA = psoriatic arthritis; PY = patient years; SAE = serious adverse event; TEAE = treatment-emergent adverse event.

NOTE: Patients with multiple occurrences of the same event are categorized by the highest severity. 

Integrated Analysis of Ixekizumab Exposures

In 4 completed and ongoing ixekizumab clinical trials for PsA, 1401 patients with active PsA have received at least 1 dose of ixekizumab, representing 2228.6 PYs of exposure as of the data cutoff of March 21, 2019.1

The numbers of TEAEs, SAEs, deaths, and discontinuations due to an AE as of March 21, 2019 are shown in Table 2.

The rate of discontinuation from study drug due to an AE was similar between all PsA ixekizumab exposures (114/1401; 8.1%) and all PsO ixekizumab exposures (490/6091; 8.0%).1

The numbers of TEAEs of special interest as of March 21, 2019 are shown in Table 3.

Table 2. Treatment-Emergent Adverse Events and Serious Adverse Events in All Treatment Periods in All Psoriatic Arthritis Ixekizumab Exposures Integrated Analysis Set1

Event, n (%) [IR]a

Pooled IXE
(N=1401; 2228.6 PYs)
b

Patients with ≥1 TEAE

1128 (80.5) [50.6]c

Patients with ≥1 SAE

133 (9.5) [6.0]

Deaths

6 (0.4) [0.3]

Discontinuation due to AE

114 (8.1) [5.1]

Abbreviations: AE = adverse event; IR = incidence rate; IXE = ixekizumab; PY = patient year; SAE = serious adverse event; TEAE = treatment-emergent adverse event.
Notes: Patients may be counted in more than one category. Patients with multiple occurrences of the same event are categorized by the highest severity. Deaths are included among SAEs and among discontinuations due to AEs.

a IR per 100 PYs.

b Data through March 21, 2019.

c The most commonly reported TEAEs (IR per 100 PYs) were nasopharyngitis (9.1), upper respiratory tract infection (unspecified: 8.3), and injection site reaction (7.0).

Table 3. Adverse Events of Special Interest in All Treatment Periods in All Psoriatic Arthritis Ixekizumab Exposures Integrated Analysis Set1

Event, n (%) [IR]a

Pooled IXE
(N=1401; 2228.6 PYs)
b

Infections

759 (54.2) [34.1]

Serious infections

28 (2.0) [1.3]

Oral candidiasis

16 (1.1) [0.7]

Injection site reactions

259 (18.5) [11.6]

Inflammatory bowel disease (unadjudicated)

4 (0.3) [0.2]c

MACE (adjudicated)

12 (0.9) [0.5]

Malignancies

15 (1.1) [0.7]

Depression

37 (2.6) [1.7]d

Abbreviations: IR = incidence rate; IXE = ixekizumab; MACE = major adverse cerebro-cardiovascular events; PY = patient year.

a The IR per 100 PYs considered exposure time as the entire time on ixekizumab.

b Data through March 21, 2019.

c The IR of adjudicated inflammatory bowel disease was 0.1.

d The rate of suicide ideation or behavior was <.01. There were no completed suicides in the psoriatic arthritis clinical studies.

The rates of TEAEs including SAEs remained stable or decreased over time with continued exposure to ixekizumab up to 3 years (see Figure 2).1

Figure 2. Incidence Rates of Select Categories of Adverse Events at 1-year Intervals Up to 3 Years of Treatment in Patients Exposed to Ixekizumab in the Psoriatic Arthritis Clinical Development Program1

Abbreviations: IBD = inflammatory bowel disease; IR = incidence rate; IXE = ixekizumab; MACE = major adverse cerebro-cardiovascular events; PBO = placebo; PsA = psoriatic arthritis; PY = patient years; SAE = serious adverse events.

a Data are IR for 0-24 weeks for the double-blind period for SPIRIT-P1 and -P2 only.

Therapeutic Indication

Ixekizumab, alone or in combination with methotrexate, is indicated for the treatment of active psoriatic arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drug (DMARD) therapies.2

References

1. Genovese MC, Kameda H, Rahman P, et al. Safety profile of ixekizumab in patients with moderate-to-severe plaque psoriasis and psoriatic arthritis: integrated analysis of 18 clinical trials. Poster presented at: American College of Rheumatology/ARP; November 8-13, 2019; Atlanta, GA.

2. Taltz [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

3. Mease P, Roussou E, Burmester GR, et al. Safety of ixekizumab in patients with psoriatic arthritis: results from a pooled analysis of three clinical trials. Arthritis Care Res (Hoboken). 2019;71(3):367-378. http://dx.doi.org/doi:10.1002/acr.23738

4. Goupille P, Roussou E, Burmester G, et al. SAT0348 Safety of ixekizumab in patients with psoriatic arthritis: results from a pooled analysis of three clinical trials [abstract]. Ann Rheum Dis. 2018;77(suppl 2):1039-1040. http://dx.doi.org/10.1136/annrheumdis-2018-eular.2132

5. Mease PJ, van der Heijde D, Ritchlin CT, et al. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis. 2017;76(1):79-87. http://dx.doi.org/10.1136/annrheumdis-2016-209709

6. Nash P, Kirkham B, Okada M, et al. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomized, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial. Lancet. 2017;389(10086):2317-2327. http://dx.doi.org/10.1016/S0140-6736(17)31429-0

7. A long-term efficacy and safety study of ixekizumab (LY2439821) in participants with active psoriatic arthritis (SPIRIT P3). ClinicalTrials.gov identifier: NCT02584855. Updated November 6, 2018. Accessed March 13, 2019. https://www.clinicaltrials.gov/ct2/show/NCT02584855?term=SPIRIT-P3&rank=1.

Glossary

AE = adverse event

AESI = adverse event of special interest

CD = Crohn's disease

EAIR = exposure adjusted incidence rate

IBD = inflammatory bowel disease

IR = incidence rate

ISR = injection site reaction

MACE - major adverse cardiovascular events

PsA = psoriatic arthritis

PsO = psoriasis

PY = patient years

SAE = serious adverse event

TEAE = treatment emergent adverse event

UC = ulcerative colitis

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

Appendix: Clinical Trial Brief Descriptions

  • SPIRIT-P1 (N=417) is a phase 3, 24-week double-blind, placebo-controlled trial with an active reference arm in patients with active PsA who are naïve to bDMARDs with an extension period of up to 3 years.5

  • SPIRIT-P2 (N=363) is a phase 3, 24-week double-blind, placebo-controlled trial in patients with active PsA and an inadequate response or intolerance to TNF inhibitor, with an extension period of up to 3 years.6

  • SPIRIT-P3 (N=570) consists of a 36-week open-label period followed by a randomized double-blind withdrawal period from week 36 to week 104. This trial is being conducted in patients naïve to bDMARDs.7

Date of Last Review: October 18, 2019

Contact Lilly

Call or Email us

If you want to ask a Medical Information question or you want to report an adverse event or product complaint you can call us or email us at ukmedinfo@lilly.com

Available Mon - Fri, 8am - 4pm, excluding Bank Holidays

Or you can

Ask us a question Chat with Us If you have a question, you can chat online with a Lilly Medical Information professional.

Submit a question